Some of bicyclic amide derivatives analogues to the compounds of the present invention have been described that they are useful as thromboxane A.sub.2 (TXA.sub.2) antagonists (Japanese Patent Publication (Kokoku) No. 53295/1991). However, in the Japanese Patent Publication (Kokoku) No. 53295/1991, it has only been described that the compounds are useful as TXA.sub.2 antagonists, but there is no suggestion of the useful thereof as PGD.sub.2 antagonists as found in the present invention. On the other hand, in Japanese Patent Publication (Kokoku) No.79060/1993, Japanese Patent Publication (Kokoku) No.23170/1994 and Chem. Pharm. Bull. Vol.37, No.6 1524-1533 (1989), it has been described bicyclic amide derivatives, which are intermediates for bicyclic sulfonamide derivatives. However, the compounds disclosed therein are different from those of the present invention in the species of substituents at the amide portion. And some of the compounds analogues to the compounds of the present invention has been described that they are useful as PGD.sub.2 antagonists in WO 97/00853. However, there is no suggestion that the compounds disclosed in WO 97/00853 possess a inhibitory activity against infiltration of eosionophils.
TXA.sub.2 has been known to have various activities such as platelet aggregation, thrombogenesis, etc. The TXA.sub.2 antagonists have therefore been considered to be useful as anti-thrombotic agents as well as drugs in the treatment of myocardial infarction or asthma.
On the other hand, the PGD.sub.2 antagonists of the present invention are useful in the improvement of conditions due to excessive production of PGD.sub.2, particularly as drugs for treating diseases in which mast cell dysfunction is involved, for example, systemic mastocytosis and disorder of systemic mast cell activation as well as for tracheal contraction, asthma, allergic rhinitis, allergic conjunctivitis, urticaria, ischemic reperfusion injury, inflammation, and atopic dermatitis.
PGD.sub.2 is a major prostanoid that is produced in and released from mast cells in which it is produced through PGG.sub.2 and PGH.sub.2 from arachidonic acid by the action of cyclooxygenase activated by immunological or unimmunological stimulation. PGD.sub.2 has various potent physiological and pathological activities. For example, PGD.sub.2 can cause strong tracheal contraction to lead to bronchial asthma, and in a systemic allergic state, it dilates the peripheral vessels to cause an anaphylactic shock. Especially, much attention has been paid to the theory that PGD.sub.2 is one of the casual substances responsible to the onset of nasal blockage in the allergic rhinitis. Therefore, it has been proposed to develop an inhibitor against the biosynthesis of PGD.sub.2 or an antagonist of PGD.sub.2 receptor as a drug for the reduction of nasal blockage. However, the inhibitor of PGD.sub.2 biosynthesis possibly much affects the synthesis of prostaglandins in other parts of organisms, and therefore, it is desirable to develop an antagonist (blocker) specific to the PGD.sub.2 receptor.